The compound 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thi ophene, known also by its generic chemical name, raloxifene, is an important member of the class of compounds known as selective estrogen receptor modulators (SERMs). That compound is disclosed and claimed in U.S. Pat. No. 4,418,068.
One synthetic route for the preparation of benzo[b]thiophenes is disclosed in U.S. Pat. Nos. 5,606,075 and 5,606,076, and involves a compound of formula ##STR2## wherein R.sup.1 and R.sup.2 are independently hydrogen, C.sub.1 -C.sub.4 alkoxy, aryloxy, halo, or amino, and R.sup.3 is a thermally labile or acid labile group. This intermediate is cyclized in the presence of an acid catalyst to form a compound of formula II ##STR3##
While this and other methods provide synthetic routes to benzo[b]thiophenes, a more efficient synthesis of benzothio[b]thiophenes is desirable. An improved synthetic route would preferably consist of fewer steps, be applicable to the preparation of 3-bromo-benzo[b]thiophenes, for example, and have milder reaction conditions. In addition, in the event that the starting materials or other reagents necessary for the processes described in the aforementioned United States patents are unavailable, it would be advantageous to have alternative commercial processes for the preparation of benzo[b]thiophenes. The present invention provides novel intermediates and novel synthetic routes for preparing intermediates, as well as for preparing substituted benzo[b]thiophenes.